Neurons contact each other mostly by synaptic transmission at synapses. Synaptic transmission is mediated by calcium-triggered vesicle fusion with the plasma membrane, which releases transmitter molecules that act on postsynaptic transmitter receptors. My goal is to improve our understanding on the cellular and molecular mechanisms underlying synaptic vesicle exocytosis, which are the building block for synaptic transmission and thus the signaling process in the neuronal network. My progress in the last year is listed in the following. First, the widely observed rapid endocytosis is generally assumed to recycle vesicles within the readily releasable pool (RRP) via a kiss-and-run mechanism that involves rapid opening and closure of a fusion pore at the release site. Here we found that rapid endocytosis do not recycle vesicles to the RRP, but to a large recycling pool (Wu &Wu, J Neurosci, 2009). This finding challenges the current model that the function of the rapid kiss-and-run fusion is to recycle vesicles rapidly within the RRP for rapid reuse. Second, we found calcium/calmodulin activates a phosphotase calcineurin, which in turn regulates vesicle cycling by which synaptic transmission is maintained during repetitive stimulation (Sun et al., J Neurosci, 2010).